Varicella zoster (V-Z) infections in patients with cancer are common and may be severe. Both adenosine arabinoside and preformed human interferon (IF) have demonstrated efficacy in established herpes infections. Currently, we are running a randomized, double-blind study in cancer patients with herpes zoster, where half the patients receive polyinosinic polycytidylic acid (Poly I:C) and the other half receive a placebo to determine whether Poly I:C can alleviate herpes zoster. To date, 40 patients have been entered on the study and 38 are evaluable. The Poly I:C treated patients had shorter times to: (1) Shut-off of new vesicles, (2) pustulation, and (3) crustation, but the differences were modest and the number in each too small for statistical evaluation. We also showed that patients with markedly depressed T-cells (500) or with grossly deficient cellular response to V-Z antigen did worse; and that patients in relapse had significantly lower IF levels both in serum and vesicle fluid and lower proliferative activity of lymphocytes to V-Z antigen when compared to patients in remission of their cancer. We have also treated three children exposed to varicella with Poly I:C during the incubation period. None of these three children developed clinical varicella. We now propose: (1) To complete the clinical randomized double-blind study in herpes zoster and (2) to study Poly I:C/Poly-L-lysine in (a) children with cancer who have been exposed to varicella and (b) in cancer patients with documented viral pneumonia. Poly I:C-LC results in much higher levels of serum IF compared to unmodified Poly I:C. (3) We also propose to develop a thiolated analog of Poly I:C for human testing which appears to avoid the hyporesponsive state following Poly I:C and thus allow the use of multiple doses of thiolated Poly I:C during a viral illness.